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At least 109 records · Page 6

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DOE OSTI2023

Neonatal Zika virus infection causes transient perineuronal net degradation

Perineuronal nets (PNNs) form a specialized extracellular matrix that predominantly surrounds parvalbumin (PV)-expressing GABAergic inhibitory interneurons and help regulate neuronal activity. Their formation early in the postnatal period is regulated by neuronal signaling and glial activation raising concerns that part of the long-term effects ascribed to perinatal viral infections could be mediated by altered PNN formation. Previously, we developed a model of neonatal Zika virus (ZIKV) infection where mice have lifelong neurological sequelae that includes motor disfunction and reduced anxiety coupled with a persistent low-grade expression in proinflammatory markers despite resolving the acute infection. Here, we demonstrate that ZIKV infection to P1 neonatal mice results in a reduction of PNN formation during the acute disease with significant reduction in Wisteria floribunda agglutinin (WFA) staining at the peak of infection [15 days post infection (dpi)] that persisted after the symptoms resolved (30 dpi). At 60 dpi, when there is residual inflammation in the CNS, the number of WFA + cells and the level of WFA staining as well as levels of aggrecan and brevican in the brains of convalescent mice were not different from those in uninfected controls, however, there was increased frequency of PNNs with an immature phenotype. Over time the impact of the perinatal infection became less evident and there were no clear differences in PNN morphology between the groups at 1 year post infection. Of note, the reduction in PNNs during acute ZIKV infection was not associated with decreased mRNA levels of aggrecan or brevican, but increased levels of degraded aggrecan and brevican indicating increased PNN degradation. These changes were associated with increased expression of matrix metalloproteinase 12 (MMP12) and MMP19, but not MMP9, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) or ADAMTS5. Together our findings indicate that infection at the time of PNN development interferes with PNN formation, but the nets can reform once the infection and inflammation subside.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Analytical model for laser-induced transient grating measurements of thermal diffusivity in non-opaque materials

The thermal transport and elastic properties of materials are often measured using the laser-induced transient grating spectroscopy (TGS) technique. The analysis of the TGS signal usually involves fitting well-known expressions, derived assuming the limiting cases of opaque or transparent materials, to the measured data. In this paper, the system of thermoelastic equations is analytically solved for an isotropic homogeneous material assuming finite laser penetration depth, which is an important consideration when the penetration depth is on the order of the acoustic wavelength. The need to use such a solution is discussed and compared to the expression for opaque material. The solution is benchmarked against TGS signal measured on single-crystal silicon with {100} surface orientation and is found to significantly improve the accuracy of the calculated thermal diffusivity as compared to using the expression for opaque material.

36 MATERIALS SCIENCE↗

NASA NTRS1983

Generalized modal shock spectra within indeterminate interface

It is noted that the generalized modal shock spectra method had limitations on the degree of structural static determinacy of the spacecraft-to-launch-vehicle interface. The 'interface modes' is used here to remove these practical limitations. The governing differential equations are derived and then shown to be valid either for integrating the modal models of two or more substructures that have been previously obtained separately or for removing a substructure from a previously available system modal model. Emphasis is placed on the integration problems in the context of the generalized modal shock spectra approach. A minimum of information the modal response of a previously obtained transient analysis of the unloaded launch vehicle is exploited in order to define an idealized modal impulse function and derive approximate explicit expressions for an estimate of the bounds of the spacecraft response. In addition, a numerical model is solved in order to compare the present results with the transient solution.

Salama, M.↗

DOE OSTI2022

Method for quantification of porcine type I interferon activity using luminescence, by direct and indirect means

Abstract Background Type I interferons are widely used in research applications and as biotherapeutics. Current assays used to measure interferon concentrations, such as plaque reduction assays and ELISA, are expensive, technically challenging, and may take days to provide results. We sought to develop a robust and rapid assay to determine interferon concentrations produced from transiently transfected cell cultures. Method Indirect quantification of recombinant interferon was evaluated using a novel bi-cistronic construct encoding the Foot-and-mouth disease virus 2A translational interrupter sequence to yield equimolar expression of Gaussia princeps luciferase and porcine interferon α. Direct quantification was evaluated by expression of a novel fusion protein comprised of Gaussia princeps luciferase and porcine type I interferon. Plasmids encoding constructs are transiently transfected into cell cultures and supernatant harvested for testing of luminescence, ELISA determined concentration, and anti-viral activity against vesicular stomatitis virus. Results Bi-cistronic constructs, utilized for indirect quantification, demonstrate both luciferase activity and anti-viral activity. Fusion proteins, utilized for direct quantification, retained secretion and luminescence however only the interferon α fusion protein had antiviral activity comparable to wildtype porcine interferon α. A strong linear correlation was observed between dilution and luminescence for all compounds over a dynamic range of concentrations. Conclusion The correlation of antiviral and luciferase activities demonstrated the utility of this approach, both direct and indirect, to rapidly determine recombinant interferon concentrations. Concentration can be determined over a more dynamic concentration range than available ELISA based assays using this methodology.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Observability of negative capacitance of a ferroelectric film: Theoretical predictions

Here, we theoretically explore mechanisms that can potentially give rise to the steady-state and transient negative capacitance in a uniaxial ferroelectric film stabilized by a dielectric layer. The analytical expressions for the steady-state capacitance of a single-domain and polydomain states are derived within the Landau-Ginzburg-Devonshire approach and used to study the state stability vs the domain splitting as a function of dielectric layer thickness. Analytical expressions for the critical thickness of the dielectric layer, polarization amplitude, equilibrium domain period, and susceptibility are obtained and corroborated by finite element modeling. Furthermore we explore the possible effects of nonlinear screening by two types of screening charges at the ferroelectric-dielectric interface and show that if at least one of the screening charges is very slow, the total polarization dynamics can exhibit complex time- and voltage-dependent behaviors that can be interpreted as an observable negative capacitance. In this setting, the transient negative capacitance effect is accompanied by almost zero dielectric susceptibility in a wide voltage range and low frequencies. These results may help to elucidate the observation of the transient negative capacitance in thin ferroelectric films, and identify materials systems that can give rise to the behavior.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

DOE OSTI2021

Incorporating concentration-dependent sediment microbial activity into methylmercury production kinetics modeling

We report in anoxic environments, anaerobic microorganisms carrying the hgcAB gene cluster can mediate the transformation of inorganic mercury (Hg(II)) to monomethylmercury (MMHg). The kinetics of Hg(II) transformation to MMHg in periphyton from East Fork Poplar Creek (EFPC) in Oak Ridge, TN have previously been modeled using a transient availability model (TAM). The TAM for Hg(II) methylation combines methylation/demethylation kinetics with kinetic expressions for processes that decrease Hg(II) and MMHg availability for methylation and demethylation (multisite sorption of Hg(II) and MMHg, Hg(II) reduction/Hg(0) oxidation). In this study, the TAM is used for the first time to describe MMHg production in sediment. We assessed MMHg production in sediment microcosms using two different sediment types from EFPC: a relatively anoxic, carbon-rich sediment with higher microbial activity (higher CO 2 production from sediment) and a relatively oxic, sandy, carbon-poor sediment with lower microbial activity (lower CO 2 production from sediment). Based on 16s rRNA sequencing, the overall microbial community structure in the two sediments was retained during the incubations. However, the hgcA containing methanogenic Euryarchaeota communities differed between sediment types and their growth followed different trajectories over the course of incubations, potentially contributing to the distinct patterns of MMHg production observed. The general TAM paradigm performed well in describing MMHg production in the sediments. However, the MMHg production and ancillary data suggested the need to revise the model structure to incorporate terms for concentration-dependent microbial activity over the course of the incubations. We modified the TAM to include Monod-type kinetics for methylation and demethylation and observed an improved fit for the carbon-rich, microbially active sediment. Overall our work shows that the TAM can be applied to describe Hg(II) methylation in sediments and that including expressions accounting for concentration-dependent microbial activity can improve the accuracy of the model description of the data in some cases.

54 ENVIRONMENTAL SCIENCES↗

NASA NTRS1982

Effects of unsteady free-stream velocity and free-stream turbulence at a stagnation point

The combined effects of transient free stream velocity and turbulence at a stagnation point on a cylinder situated in a crossflow is investigated analytically, and a model is formulated for the eddy diffusivity induced by free-stream turbulence. The steepest descent method is used to integrate the governing momentum expression, and numerical solutions are given for the unsteady wall shear stress function for specific free-stream transients. It is found after correlation of the results by means of a new turbulence parameter that wall friction increases with increasing free-stream turbulence intensity, and that the friction factor increases with increasing reduced frequency of oscillation values.

Gorla, R. S. R.↗

NASA NTRS1958

A simplified method for approximating the transient motion in angles of attack and sideslip during a constant rolling maneuver

The transient motion in angles of attack and sideslip during a constant rolling maneuver has been analyzed. Simplified expressions are presented for the determination of the pertinent modes of motion as well as the modal coefficient corresponding to each mode. Calculations made with and without the derivatives for side force due to sideslip and lift-curve slope indicate that although these derivatives increase the total damping of the system they do not markedly affect the transient motion.

Sternfield, Leonard↗

DOE OSTI2021

The effect of a transducer’s spatial averaging on an elastodynamic guided wave’s wavenumber spectrum

Elastodynamic guided waves propagate in an elastic solid which makes it difficult, if not impractical, to place a receiving transducer in the direct path of the propagating wave (as one would for an acoustic wave in a fluid medium). Thus, to account for this, receiving transducers are often placed on the surface of the solid waveguide such that the transducer surface is parallel to the wave propagation direction. This transducer orientation introduces spatial averaging, which causes the received signal to have an altered signal amplitude and mode bias. We investigate both of these effects and present a simple model from which we derive a scaling-ratio expression that describes the effects of spatial averaging. Furthermore, we then test its performance using finite-element simulations that incorporate “real-world” assumptions (e.g., transient waves, piezoelectric effects, etc.). The results from the simulations demonstrate that the scaling-ratio can characterize the effects resulting from spatial averaging. The scaling-ratio expression will be particularly useful when designing experiments involving high frequency (small wavelength) guided waves. Lastly, the proposed scaling-ratio expression could be applied to other sensing methods, like Laser Doppler Vibrometry (LDV) or piezoelectric waveguides with inter-digitated transducers, because of its generality. However, the authors are careful to note that the scaling-ratio expression is not intended as a replacement of multi-physics analysis or good experimental design, and the effects of spatial averaging should be avoided whenever possible.

2DFFT↗

NASA NTRS1993

Molecular Basis of the Increase in Invertase Activity Elicited by Gravistimulation of Oat-Shoot Pulvini

An asymmetric (top vs. bottom) increase in invertase activity is elicited by gravistimulation in oatshoot pulvini starting within 3h after treatment. In order to analyze the regulation of invertase gene expression in this system, we examined the effect of gravistimulation on invertase mRNA induction. Total RNA and poly(A)(+)RNA, isolated from oat pulvini, and two oligonucleotide primers, corresponding to two conserved amino-acid sequences (NDPNG and WECPD) found in invertase from other species, were used for the Polymerase Chain Reaction (PCR). A partial-length cDNA (550 base pairs) was obtained and characterized. There was a 52 % deduced amino-acid sequence homology to that of carrot beta-fructosi- dase and a 48 % homology to that of tomato invertase. Northern blot analysis showed that there was an obvious transient accumulation of invertase mRNA elicited by gravistimulation of oat pulvini. The mRNA was rapidly induced to a maximum level at 1h following gravistimulation treatment and gradually decreased afterwards. The mRNA level in the bottom half of the oat pulvinus was significantly higher (five-fold) than that in the top half of the pulvinus tissue. The induction of invertase mRNA was consistent with the transient enhancement of invertase activity during the graviresponse of the pulvinus. These data indicate that the expression of the invertase gene(s) could be regulated by gravistimulation at the transcriptional and/or translational levels. Southern blot analysis showed that there were four genomic DNA fragments hybridized to the invertase cDNA. This suggests that an invertase gene family may exist in oat plants.

Wu, Liu-Lai↗

DOE OSTI2025

Stochastic fluctuations and the relaxation time in transient relativistic fluids

We argue that the ratio between the shear viscosity and the shear relaxation time, η/τ π , should be defined as a thermodynamic quantity obtained from the equal-time symmetric correlator of the shear-stress tensor. In kinetic theory, we show that this ratio does not depend on the type of interaction. Similarly, an exact expression for this ratio is obtained for holographic gauge theories. We also determine how stochastic fluctuations change η/τ π in transient relativistic hydrodynamics and show that thermal fluctuations do not spoil causality and stability.

Denicol, Gabriel S. [Universidade Federal Fluminen↗

NASA NTRS1969

Thermal Network Analyzer Program

Computer program solves transient or steady-state heat flow problems through the concept of lumped parameters expressed as the electrical analog of the heat transfer problem using finite differences techniques.

Sakakura, H. D.↗

NASA NTRS1999

Rapid and systemic accumulation of chloroplast mRNA-binding protein transcripts after flame stimulus in tomato

It has been shown that tomato (Lycopersicon esculentum) plants respond to flame wounding and electrical stimulation by a rapid (15 min) and systemic up-regulation of proteinase inhibitor (pin) genes. To find other genes having a similar expression pattern, we used subtractive cDNA screening between flamed and control plants to select clones up-regulated by flame wounding. We report the characterization of one of them, a chloroplast mRNA-binding protein encoded by a single gene and expressed preferentially in the leaves. Systemic gene expression in response to flaming in the youngest terminal leaf exhibited three distinct phases: a rapid and transient increase (5-15 min) in transcript accumulation, a decline to basal levels (15-45 min), and then a second, more prolonged increase (60-90 min). In contrast, after a mechanical wound the rapid, transient increase (5 min) was followed by a rapid decline to basal levels but no later, prolonged accumulation. In the petiole, the initial flame-wound-evoked transient increase (15 min) was followed by a continuous decline for 3 h. The nature of the wound signal(s) causing such rapid changes in transcript abundance is discussed in relation to electrical signaling, which has recently been implicated in plant responses to wounding.

NASA Discipline Plant Biology↗

NASA NTRS1993

Mixing and transient interface condensation of a liquid hydrogen tank

Experiments were conducted to investigate the effect of axial jet-induced mixing on the pressure reduction of a thermally stratified liquid hydrogen tank. The tank was nearly cylindrical, having a volume of about 0.144 cu m with 0.559 m in diameter and 0.711 m length. A mixer/pump unit, which had a jet nozzle outlet of 0.0221 m in diameter was located 0.178 m from the tank bottom and was installed inside the tank to generate the axial jet mixing and tank fluid circulation. Mixing tests began with the tank pressures at which the thermal stratification results in 4.9-6.2 K liquid subcooling. The mixing time and transient vapor condensation rate at the liquid-vapor interface are determined. Two mixing time correlations, based on the thermal equilibrium and pressure equilibrium, are developed and expressed as functions of system and buoyancy parameters. The limited liquid hydrogen data of the present study shows that the modified steady state condensation rate correlation may be used to predict the transient condensation rate in a mixing process if the instantaneous values of jet sub cooling and turbulence intensity at the interface are employed.

Lin, C. S.↗

DOE OSTI2022

Structural mechanism of allosteric activation of TRPML1 by PI(3,5)P 2 and rapamycin

Transient receptor potential mucolipin 1 (TRPML1) is a Ca 2+ -permeable, nonselective cation channel ubiquitously expressed in the endolysosomes of mammalian cells and its loss-of-function mutations are the direct cause of type IV mucolipidosis (MLIV), an autosomal recessive lysosomal storage disease. TRPML1 is a ligand-gated channel that can be activated by phosphatidylinositol 3,5-bisphosphate [PI(3,5)P 2 ] as well as some synthetic small-molecule agonists. Recently, rapamycin has also been shown to directly bind and activate TRPML1. Interestingly, both PI(3,5)P 2 and rapamycin have low efficacy in channel activation individually but together they work cooperatively and activate the channel with high potency. To reveal the structural basis underlying the synergistic activation of TRPML1 by PI(3,5)P 2 and rapamycin, we determined the high-resolution cryoelectron microscopy (cryo-EM) structures of the mouse TRPML1 channel in various states, including apo closed, PI(3,5)P 2 -bound closed, and PI(3,5)P 2 /temsirolimus (a rapamycin analog)-bound open states. These structures, combined with electrophysiology, elucidate the molecular details of ligand binding and provide structural insight into how the TRPML1 channel integrates two distantly bound ligand stimuli and facilitates channel opening.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1993

Kinetic Induction of Oat Shoot Pulvinus Invertase mRNA by Gravistimulation and Partial cDNA Cloning by the Polymerase Chain Reaction

An asymmetric (top vs. bottom halves of pulvini) induction of invertase mRNA by gravistimulation was analyzed in oat shoot pulvini. Total RNA and poly(A)(+) RNA, isolated from oat pulvini, and two oli-gonucleotide primers, corresponding to two conserved amino acid sequences (NDPNG and WECPD) found in invertase from other species, were used for the polymerase chain reaction (PCR). A partial length cDNA (550 bp) was obtained and characterized. A 62% nucleotide sequence homology and 58% deduced amino acid sequence homology, as compared to beta-fructosidase of carrot cell wall, was found. Northern blot analysis showed that there was an obviously transient induction of invertase mRNA by gravistimulation in the oat pulvinus system. The mRNA was rapidly induced to a maximum level at 1 hour after gravistimulation treatment and gradually decreased afterwards. The mRNA level in the bottom half of the oat pulvinus was significantly higher than that in the top half of the pulvinus tissue. The kinetic induction of invertase mRNA was consistent with the transient accumulation of invertase activity during the graviresponse of the pulvinus. This indicates that the expression of the invertase gene(s) could be regulated by gravistimulation at the transcriptional level. Southern blot analysis showed that there were two to three genomic DNA fragments which hybridized with the partial-length invertase cDNA.

Wu, Liu-Lai↗

NASA NTRS2010

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions.

Crucian, B. E.↗

NASA NTRS1993

Mixing and transient interface condensation of a liquid hydrogen tank

Experiments were conducted to investigate the effect of axial jet-induced mixing on the pressure reduction of a thermally stratified liquid hydrogen tank. The tank was nearly cylindrical, having a volume of about 0.144 cu m with 0.559 m in diameter and 0.711 m long. A mixer/pump unit, which had a jet nozzle outlet of 0.0221 m in diameter was located 0.178 m from the tank bottom and was installed inside the tank to generate the axial jet mixing and tank fluid circulation. The liquid fill and jet flow rate ranged from 42 to 85 percent (by volume) and 0.409 to 2.43 cu m/hr, respectively. Mixing tests began with the tank pressure ranging from 187.5 to 238.5 kPa at which the thermal stratification results in 4.9 to 6.2 K liquid sub cooling. The mixing time and transient vapor condensation rate at the liquid-vapor interface are determined. Two mixing time correlations, based on the thermal equilibrium and pressure equilibrium, are developed. Both mixing time correlations are expressed as functions of system and buoyancy parameters and compared well with other experimental data. The steady state condensation rate correlation of Sonin et al. based on steam-water data is modified and expressed as a function of jet subcooling. The limited liquid hydrogen data of the present study shows that the modified steady state condensation rate correlation may be used to predict the transient condensation rate in a mixing process if the instantaneous values of jet sub cooling and turbulence intensity at the interface are employed.

Lin, C. S.↗